prediction of the therapeutic response in depression based on neuro-computational modeling assessment of motivation

Conditions: Major Depressive Disorder

Summary: this study aims to better understand the mechanisms of action of antidepressants, but also the neural correlates of motivation deficits. one hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. the objective will be to predict the therapeutic response to two first-line antidepressants on the basis of an early neurocomputational assessment of motivation. antidepressant treatment will be administered as monotherapy after randomization between two drugs: escitalopram and vortioxetine. patients will undergo six visits and follow-up for one year. the investigators will combine computer modeling and functional mri to identify motivational deficits and elucidate their brain correlates before initiation, after 7 days and after 6 months of treatment. 36 healthy volunteers will also be included to allow comparison with patients with depression. they will not receive any treatment.

one hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. six visits will be scheduled within a year: * v0 (inclusion visit): verification of inclusion and exclusion criteria, information, and consent. * v1 (before randomization - baseline state): * clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction. * neuro-cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating. part of the tests will be performed during the functional mri session. * structural (anatomical) and functional mri, asl. * blood samples. * randomization and introduction of the new antidepressant will occur immediately after v1. to maximize acceptability by referring psychiatrists, dosage and co-prescriptions will be at the discretion of the psychiatrist in charge, but the assigned treatment will not be changed for 4 weeks (until v3). * v2 (7 days after the beginning of the new antidepressant - 'early response visit'): o similar to v1. * v3 (28 days after the beginning of the new antidepressant - 'conventional response visit'): * clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction. * blood samples * v4 (6 months after the beginning of the new antidepressant - 'remission visit'): * clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction. * cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating. * structural (anatomical) mri, asl * blood samples * v5 (one year after the beginning of the new antidepressant - 'functional remission visit'): * clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction. 36 healthy volunteers without a history of neurologic or psychiatric disorder, matched for age, gender, and education will be included. they will perform v0-v2 (without mri and blood sample at v2). healthy volunteers will not receive any treatment as part of the research.

Eligibility criteria:
patients with major depressive disorder inclusion criteria: * meeting dsm-5 criteria for major depressive disorder (single or recurrent episodes) * with a madrs score \>= 24 * for which a new line of treatment is needed * no previous line of antidepressant for this episode or wash-out long-enough to avoid carry-over effects * valid health care insurance exclusion criteria: * treatment-resistant depression (defined as insufficient response despite at least 2 trials of antidepressant prescribed at adequate dose and duration) * subjects with a trial of escitalopram and/or vortioxetine for the current episode, or with contra-indication to one of these two drugs * subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation). * subject with a history of neurological disorder: parkinson's disease, dementia * contraindications to mri scanning: pregnancy, claustrophobia, metallic implants * pregnant or breastfeeding women * involuntary hospitalisation and legal protection measures healthy volunteers inclusion criteria: - valid health care insurance exclusion criteria: * subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation). * subject with a history of neurological disorder: parkinson's disease, dementia * contraindications to mri scanning: pregnancy, claustrophobia, metallic implants * pregnant or breastfeeding women